Mild Cognitive ImpairmentNCT05907343
Closed-Loop Brain Stimulation as a Potential Intervention for Cognitive Decline
A study testing Closed-loop TBS and Open-loop TBS in people with Mild Cognitive Impairment and Alzheimer Dementia (AD), run by University of Texas at Austin at 1 site in United States.
Trial summary
The goal of this clinical study is to investigate the effectiveness of non-invasive stimulation to enhance cognitive control abilities in older adults with and without cognitive impairment. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Dementia (AD)
- What is being tested?
- Closed-loop TBS and Open-loop TBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- 31 May 2023to 31 Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Older adults
- Ages between 60 to 90 years
- Good general health
- Normal or corrected vision
- Completed elementary school education or able to understand middle school level experiment instructions
- Self reports cognitive complaints
Show all 11Show fewer
- Cognitively normal young adults
- Ages between 18 to 35 years
- Good general health
- Normal or corrected vision
- Completed elementary school education or able to understand middle school level experiment instructions
Who cannot join
- Self-report of neurological or psychiatric diseases that could be contraindicated for TMS (e.g., personal history of epilepsy/seizure brain damage, history of fainting, bipolar disorder, schizophrenia, current substance use disorder, etc.).
- Medications that elevate seizure threshold (e.g., stimulant medication, high dose bupropion).
- Factors hindering EEG acquisition and rTMS delivery (e.g., skin infection, wounds, dermatitis, unable to access the scalp of the participant (e.g., unremovable wig).
- Current participation in amyloid infusion treatment for Alzheimer's disease.
- Do not have the capacity to provide informed consent and does not have a Legally Authorized Representative.
- Resting motor threshold below the power limit in the laboratory. (Will be check on the first visit)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Health Discovery Building
Austin, Texas, 78712
Patrick Escamilla, 512-495-5246, pescamilla@austin.utexas.edu
About this study
The goal of this clinical study is to investigate the effectiveness of non-invasive stimulation to enhance cognitive control abilities in older adults with and without cognitive impairment. The main questions it aims to answer are:
- whether it is possible to restore various cognitive functions in older adults by delivering theta burst stimulation (TBS), a form of transcranial magnetic stimulation, and
- whether closed-loop TBS is able to induce therapeutic benefits that outperform open-loop TBS.
Read more
Participants play a cognitive video game while a brain-computer interface (BCI) analyzes their electroencephalogram (EEG) signals and decodes the presence or absence of the contingent negative variation (CNV) potential, a marker of cognitive control. The BCI triggers TBS when its outputs indicate that the participant is not engaged properly in the video game.
Researchers will compare the effects of closed-loop and open-loop TBS using the outcome metrics described below to see how much cognitive restorations is achievable with each stimulation modality.
- Conditions
- Mild Cognitive Impairment, Alzheimer Dementia (AD)
- Being tested
- Closed-loop TBS, Open-loop TBS
- Keywords
- MCI, Older adults, Cognitive control, Memory impairment, Memory enhancement
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease, Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-loop TBSDevice
A BCI records and analyzes the participant's EEG as they perform cognitively demanding video game tasks. The BCI delivers TBS with a real coil when its output indicates that the participant is not properly engaged in the video game.
Open-loop TBSDevice
A BCI records and analyzes the participant's EEG as they perform cognitively demanding video game tasks. TBS with the real coil is delivered irrelevant of the BCI decoder output.
| Study group | Role | What they receive |
|---|---|---|
| Closed-Loop TBS | Active comparator | Not described Receives: Device: Closed-loop TBS |
| Open-Loop TBS | Active comparator | Not described Receives: Device: Open-loop TBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Assessment Batteries
NIH Toolbox - Cognition Battery: A computerized battery assessing multiple cognitive domains. The primary metric for all subtests is the age- and education-adjusted T-score (normative mean = 50, standard deviation = 10).
Includes: Dimensional Change Card Sort, Face-Name Associative Memory Test, Flanker Inhibitory Control and Attention Test, Picture Sequence Memory Test, Rey Auditory Verbal Learning Test, Pattern Comparison Processing Speed Test
Measured: Up to 8 weeks after intervention
Secondary outcomes (6)
Accuracy of the BCI classifier output
The BCI classifier output reflects the presence or absence of the cognitive EEG patterns elicited during the cognitive videogame tasks. For each participant, the BCI outputs will be compared to their behavioral responses (pressing or not pressing a button).
Measured: Up to 8 weeks after intervention
Behavioral performance of the video game task
The behavioral performance, pressing or not pressing a button, reflects the level of cognitive control performance of the subjects. It measures whether the participants made a correct decision, and their response time, in a given trial.
Measured: Up to 8 weeks after intervention
N-Back Task
Measures working memory capacity and executive function. The primary metrics are accuracy (percentage of correct responses) and reaction time during the n-back conditions.
Measured: Up to 8 weeks after intervention.
Affective Flexibility Task
Measures the ability to shift cognitive sets in response to emotional versus non-emotional stimuli. The primary metric is the switch cost (the difference in reaction time and accuracy between repeat and switch trials).
Measured: Up to 8 weeks after intervention
Perseverative Thinking Questionnaire
A 15-item self-report scale measuring transdiagnostic repetitive negative thinking (rumination and worry). Items are rated from 0 (never) to 4 (almost always). The primary metric is the total PTQ score (range 0-60).
Measured: Up to 8 weeks after intervention
Hamilton Depression Rating Scale
A interview assessing the severity of depressive symptomatology (e.g., mood, insomnia, anxiety). The primary metric is the total score, with higher scores indicating greater severity.
Measured: Up to 8 weeks after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start31 May 2023
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas at Austin
- Sponsor type
- University, hospital or other
- Collaborators
- Texas Alzheimer's Research and Care Consortium
- Responsible party
- Principal investigator, Jose del R. Millan, University of Texas at Austin
- Investigators
- José del R. Millán, PhD, Principal investigator, University of Texas at AustinJared F. Benge, PhD, ABPP, Principal investigator, University of Texas at AustinCrystal M. Lantrip, PhD, LP, Principal investigator, Neuropsychological Assessment Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05907343
- Sponsor's protocol ID
- STUDY00003055
- Status last verified
- Aug 2026
- First submitted
- 7 Jun 2023
- Last updated
- 2 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: All anonymized data will be made available by the online publication date. These data will be placed in public servers for any interested researcher to access it.
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-Loop Brain Stimulation as a Potential Intervention for Cognitive Decline
- ClinicalTrials.gov ID
- NCT05907343
- Acronym / sponsor ID
- STUDY00003055
- Conditions
- Mild Cognitive Impairment, Alzheimer Dementia (AD)
- Keywords
- MCI, Older adults, Cognitive control, Memory impairment, Memory enhancement
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- University of Texas at AustinUniversity, hospital or other
- Collaborators
- Texas Alzheimer's Research and Care Consortium
- Study start
- 31 May 2023 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 18 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical study is to investigate the effectiveness of non-invasive stimulation to enhance cognitive control abilities in older adults with and without cognitive impairment. The main questions it aims to answer are:
- whether it is possible to restore various cognitive functions in older adults by delivering theta burst stimulation (TBS), a form of transcranial magnetic stimulation, and
- whether closed-loop TBS is able to induce therapeutic benefits that outperform open-loop TBS.
Participants play a cognitive video game while a brain-computer interface (BCI) analyzes their electroencephalogram (EEG) signals and decodes the presence or absence of the contingent negative variation (CNV) potential, a marker of cognitive control. The BCI triggers TBS when its outputs indicate that the participant is not engaged properly in the video game.
Researchers will compare the effects of closed-loop and open-loop TBS using the outcome metrics described below to see how much cognitive restorations is achievable with each stimulation modality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Closed-Loop TBS | Active comparator | Device: Closed-loop TBS |
| Open-Loop TBS | Active comparator | Device: Open-loop TBS |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Older adults
- Cognitively normal young adults
Key exclusion criteria (6 listed)
- Self-report of neurological or psychiatric diseases that could be contraindicated for TMS (e.g., personal history of epilepsy/seizure brain damage, history of fainting, bipolar disorder, schizophrenia, current substance use disorder, etc.).
- Medications that elevate seizure threshold (e.g., stimulant medication, high dose bupropion).
- Factors hindering EEG acquisition and rTMS delivery (e.g., skin infection, wounds, dermatitis, unable to access the scalp of the participant (e.g., unremovable wig).
- Current participation in amyloid infusion treatment for Alzheimer's disease.
- Do not have the capacity to provide informed consent and does not have a Legally Authorized Representative.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Closed-loop TBSA BCI records and analyzes the participant's EEG as they perform cognitively demanding video game tasks. The BCI delivers TBS with a real coil when its output indicates that the participant is not properly engaged in the video game. | Device | Closed-Loop TBS |
| Open-loop TBSA BCI records and analyzes the participant's EEG as they perform cognitively demanding video game tasks. TBS with the real coil is delivered irrelevant of the BCI decoder output. | Device | Open-Loop TBS |
Primary outcome
Cognitive Assessment Batteries
Time frame: Up to 8 weeks after intervention
NIH Toolbox - Cognition Battery: A computerized battery assessing multiple cognitive domains. The primary metric for all subtests is the age- and education-adjusted T-score (normative mean = 50, standard deviation = 10). Includes: Dimensional Change Card Sort, Face-Name Associative Memory Test, Flanker Inhibitory Control and Attention Test, Picture Sequence Memory Test, Rey Auditory Verbal Learning Test, Pattern Comparison Processing Speed Test
6 secondary outcomes
Accuracy of the BCI classifier output
Time frame: Up to 8 weeks after intervention
Behavioral performance of the video game task
Time frame: Up to 8 weeks after intervention
N-Back Task
Time frame: Up to 8 weeks after intervention.
Affective Flexibility Task
Time frame: Up to 8 weeks after intervention
Perseverative Thinking Questionnaire
Time frame: Up to 8 weeks after intervention
Hamilton Depression Rating Scale
Time frame: Up to 8 weeks after intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: Yes. All anonymized data will be made available by the online publication date. These data will be placed in public servers for any interested researcher to access it.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
José del R. Millán, PhD principal investigator
University of Texas at Austin
Jared F. Benge, PhD, ABPP principal investigator
University of Texas at Austin
Crystal M. Lantrip, PhD, LP principal investigator
Neuropsychological Assessment Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Closed-loop TBS and Open-loop TBS in people with Mild Cognitive Impairment and Alzheimer Dementia (AD), run by University of Texas at Austin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact José del R. Millán, PhD (512-232-8111, jose.millan@austin.utexas.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Assessment Batteries (time frame: Up to 8 weeks after intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.